Confirmation of linkage between juvenile myoclonic epilepsy locus and the HLA region of chromosome 6

Abstract

Juvenile myoclonic epilepsy (JME) is a generalized, non-progressive epilepsy characterized by an adolescent onset of sudden, involuntary myoclonic jerks. Greenberg et al. (American Journal of Medical Genetics 31:185-192, 1988b; Cytogenetics and Cell Genetics 51:1008, 1989b) reported tight linkage of a JME locus to the HLA region of chromosome 6p. We confirm this linkage assignment, although at a larger recombination fraction than previously reported. Twenty-three, mostly nuclear, families were ascertained through a JME proband. The affected status of relatives of the probands was assigned by 4 different clinical criteria, and separate analyses were done assuming an autosomal dominant model with 90% penetrance and an autosomal recessive model with full penetrance. A linear age-of-onset correction with maximum penetrance at age 20 years was incorporated into the analyses. The maximum lod score obtained was 3.11 at (-)m = 0.001, (-)f = 0.20, assuming autosomal dominant inheritance and using the second definition of the disease phenotype. There was strong support for linkage using the other phenotype definitions and the autosomal dominant model, although the lod scores did not exceed 3.0. There was also support for linkage of a JME locus to this region under the autosomal recessive model, although the results varied depending upon the definition of the disease phenotype. There was no significant evidence for linkage heterogeneity.

Acute Cocaine-Induced Seizures Differential Sensitivity of Six Inbred Mouse Strains

“…Paralleling this are studies documenting substantial genetic influences in human epilepsy ; Leppert et al 1991;Weissbecker et al 1991;Greenberg et al 1992).…”

The Genetics of Common Epilepsy Disorders: Lessons Learned from the Channelopathy Era

“…Several studies have published strong linkage signals for relatively large samples of families with more common forms of epilepsy [72][73][74][75][76][77]. It is almost certain that there are genes with large effects for common epilepsies.…”

“…Another connection between neural development and a common idiopathic epilepsy comes from BRD2, which is genetically linked to JME (LOD = 4.2) and to the epileptiform EEGs seen interictally both in JME patients and in some family members without seizures [72,73,85]. BRD2 on chromosome 6p21 was the first identified locus for a common epilepsy.…”

High-Resolution Mapping and Transcript Identification at the Progressive Epilepsy with Mental Retardation Locus on Chromosome 8p

“…To date, seven independent loci have been genetically mapped for monogenic forms of epilepsy with clear Mendelian patterns of inheritance (Leppert et al 1989;Lehesjoki et al 1991;Lewis et al 1993;Tahvanainen et al 1994;Ottman et al 1995;Phillips et al 1995;Guipponi et al 1997). A subset of families for one of the multifactorial forms of epilepsy, juvenile myoclonic epilepsy, may be linked to chromosome 6p (Greenberg et al 1988;Durner et al 1991;Weissbecker et al 1991;Liu et al 1995). Moreover, evidence for involvement of a locus on chromosome 8q in idiopathic generalized epilepsy has been reported (Zara et al 1995).…”